Innovative phage lysin HY-133 enters phase I clinical study

HYpharm’s innovative preventive agent HY-133 has reached the first clinical trial phase. HY-133 is specifically effective against the bacterial pathogen Staphylococcus aureus including multi-resistant strains (MRSA, methicillin-resistant S. aureus) and is intended to combat its colonisation in the nose. The active substance was further developed for use in clinical trials by HYpharm together with university partners in Greifswald, Tübingen and Munich and with the support of the DZIF (German Centre for Infection Research).

In the phase I clinical trial, conducted at the Immundermatology Study Center with the University Hospital of Tübingen as sponsor of the clinical trial, safety and toxicity of the novel drug candidate is being investigated in healthy volunteers.

At the German Center for Infection Research (DZIF), scientists from the universities of Tübingen, Greifswald (former Münster) and Munich joined forces with the company HYpharm to prepare the clinical testing of an active substance against the pathogen Staphylococcus aureus: A highly effective protein made from bacteria-specific viruses, known as bacteriophages, is designed to kill these bacteria within a very short time. The natural microbiota remains intact. The prophylactic treatment of nasal colonization could counteract the spread of multi-resistant, so-called methicillin-resistant S. aureus (MRSA) strains, in particular in hospitals, and prevent infections by this microbe in patients.

Nasal cavity

Approximately one in three people harbor the bacterium S. aureus in their nasal cavity. What is harmless in normal life quickly becomes a problem during a hospital stay. This is because the pathogens can get into wounds during operations, for example, and trigger dangerous infections. There is also the risk of the pathogen spreading as a hospital germ. The so-called methicillin-resistant Staphylococcus aureus germs, or MRSA for short, are particularly feared, as they are insensitive to many of the antibiotics commonly used.

“Rapid detection and effective elimination of MRSA colonization of the nasal cavity before a hospital stay is a decisive step in the fight against these hospital germs,” says Prof. Dr. Karsten Becker from the University Medicine Greifswald. The bacteria in the nose are increasingly insensitive to the antibiotic mupirocin, which is currently used in hospitals, and the duration of “sanitation” and monitoring of its success is around one week. This means that effective MRSA prevention is not possible for patients who need to be operated on quickly.

Phage lysin

Together with HYpharm GmbH in Bernried and with funding from the BMBF, scientists have developed a special type of active substance in recent years and investigated its effect: a phage lysin, i.e. a protein from viruses that infect bacteria, specifically attacks S. aureus cells and dissolves them. The protein was produced artificially and optimized as a “designer protein” under the name HY-133. “We are proud to have reached the milestone of approval for clinical phase I for our innovative approach and are convinced that a large number of patients will benefit from it in the future,” explains Managing Director Dr. Ingrid Wanninger from HYpharm GmbH.

Following extensive laboratory tests by Prof. Dr. Evgeny A. Idelevich and Prof. Dr. Karsten Becker at the Institute of Medical Microbiology in Greifswald, HY-133 was prepared for clinical testing in cooperation with microbiologist Prof. Dr. Andreas Peschel, Tübingen, who coordinates the research area “Hospital Germs and Antibiotic-Resistant Bacteria” at the DZIF. The substance is now ready for clinical testing and the DZIF has provided more than 5.0 million euros for formulation development by pharmacist Prof. Dr. Gerhard Winter from the LMU Munich, GMP-production, preclinical testing and finally clinical phase I testing.

As part of the Phase I clinical trial, the rapid sanitation of S. aureus strains in the nasal flora of volunteers and its influence on the nasal microbiome is being investigated. “In addition to new antibiotics and vaccines, we urgently need specific active substances to clean up problem germs. The HY-133 protein is a highly innovative active ingredient for this purpose and can become a game changer for the sanitation of nasal vestibules colonized with S. aureus and MRSA, respectively, due to its rapid effectiveness within one day,” explains Dr. Dr. Sebastian Volc as the responsible study physician in Tübingen.